Anisotropic energy flow and allosteric ligand binding in albumin

Abstract

Allosteric interactions in proteins generally involve propagation of local structural changes through the protein to a remote site. Anisotropic energy transport is thought to couple the remote sites, but the nature of this process is poorly understood. Here, we report the relationship between energy flow through the structure of bovine serum albumin and allosteric interactions between remote ligand binding sites of the protein. Ultrafast infrared spectroscopy is used to probe the flow of energy through the protein backbone following excitation of a heater dye, a metalloporphyrin or malachite green, bound to different binding sites in the protein. We observe ballistic and anisotropic energy flow through the protein structure following input of thermal energy into the flexible ligand binding sites, without local heating of the rigid helix bundles that connect these sites. This efficient energy transport mechanism enables the allosteric propagation of binding energy through the connecting helix structures.

Site‐Resolved Observation of Vibrational Energy Transfer Using a Genetically Encoded Ultrafast Heater

“…These studies have led to the proposal of transfer pathways connecting allosterically coupled sites. [2,12,13] In the few proteins investigated thus far, an on-covalently adsorbed dye [14] or the native cofactor of aheme protein [15,16] have been used as VET donors.Inorder to map VET pathways in awide range of proteins,t he ability to introduce vibrational energy at defined positions is crucial-a requirement that can be fulfilled by aVET donor in the form of anon-canonical amino acid (ncAA). Amain reason is the lack of suitable VET donor-sensor pairs to efficiently and siteselectively inject vibrational energy and to probe its transfer.…”

Allosteric Communication Pathways and Thermal Rectification in PDZ-2 Protein: A Computational Study

“…This phenomenon is involved in crucial cellular and physiological functions and is determinant in human diseases. [1][2][3] Allosteric communication can mediate signal transmission through proteins on both short (3 Å) and long (100 Å) range scales, and is studied using both experimental [4][5][6][7][8][9][10][11][12] and theoretical 8,[13][14][15][16][17][18][19] techniques, and its occurrence has been clearly established.…”

Fast infrared spectroscopy of protein dynamics: advancing sensitivity and selectivity

“…NMR spectroscopy can elucidate dynamics on many timescales, even down into the picosecond regime, but it does so via relaxation experiments, which works only for equilibrium fluctuations. With "direct time resolution", we have in mind to study non-equilibrium processes in a pump-probe fashion, such as the triggered (un)folding of a protein [4][5][6][7][8][9][10][11] or the propagation of a perturbation through an allosteric system [12][13][14]. The direct time resolution of a spectroscopic method is dictated by the dephasing time of its transitions, which is a few picoseconds for typical vibrational bands in the solution phase, in contrast to millisecond dephasing of NMR.…”